Archives of Academic Emergency Medicine. 2022; 10(1): e84 REV I EW ART I C L E Effect of Virtual Reality-Based Interventions on Pain Dur- ing Wound Care in Burn Patients; a Systematic Review and Meta-Analysis Narges Norouzkhani1, Raziyeh Chaghian Arani2, Hamidreza Mehrabi3, Parissa Bagheri Toolaroud4, Pooyan Ghorbani Vajargah5,6, Amirabbas Mollaei5,6, Seyed Javad Hosseini7, Mahbobeh Firooz7, Atefeh Falakdami5,6, Poorya Takasi5,6, Alireza Feizkhah5,8, Hessamoddin Saber5, Haniye Ghaffarzade5, Ava Nemalhabib5, Alborz Ghaffari5, Joseph Osuji9, Mohammadreza Mobayen5∗, Samad Karkhah5,6,10 † 1. Department of Medical Informatics, faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Student Research Committee, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran. 3. Student Research Committee, School of Nursing and Midwifery, Guilan University of Medical Sciences, Rasht, Iran. 4. Health Information Management Research Center, Kashan University of Medical Sciences, Kashan, Iran. 5. Burn and Regenerative Medicine Research Center, Guilan University of Medical Sciences, Rasht, Iran. 6. Department of Medical-Surgical Nursing, School of Nursing and Midwifery, Guilan University of Medical Sciences, Rasht, Iran. 7. Department of Nursing, Esfarayen Faculty of Medical Sciences, Esfarayen, Iran. 8. Department of Medical Physics, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. 9. School of Nursing and Midwifery, Faculty of Health, Community, and Education, Mount Royal University, Calgary, Ab, Canada. 10.Quchan School of Nursing, Mashhad University of Medical Sciences, Mashhad, Iran. Received: July 2022; Accepted: August 2022; Published online: 24 October 2022 Abstract: Introduction: Burn patients undergo daily painful wound care procedures, including washing, debridement, and dressing. This systematic review and meta-analysis aimed to examine the effect of virtual reality (VR)-based interventions on pain during wound care in burn patients. Methods: A comprehensive systematic search was conducted on international electronic databases such as Scopus, PubMed, and Web of Science with keywords extracted from Medical Subject Headings such as "Virtual reality", "Virtual reality therapy", "Virtual reality expo- sure therapy", "Virtual reality immersion therapy", "Exergaming”, “Active-video gaming”, “Burns”, “Wound heal- ings”, “Pain”, and “Pain management” from the earliest to May 6, 2022. The Joanna Briggs Institute ( JBI) critical appraisal checklist was used to assess the quality of randomized control trials and quasi-experimental studies. Results: 1,293 patients with burns were included in 30 studies, and their mean age was 22.89 (SD=7.63) years. 70.72% of the participants were male, and 67.05% were in the intervention group. This meta-analysis showed that VR significantly decreased pain severity in the intervention group compared to the control group (standard mean difference (SMD): -0.70, 95%CI: -0.97 to -0.43, Z=5.05, P<0.001, I2:82.0%). Immersive VR intervention showed statistically significant effects in reducing pain intensity among the intervention group, compared to the control group (SMD: -0.73, 95%CI: -0.97 to -0.49, Z=5.88, P<0.001, I2:69.3%); however, this finding was not the same for non-immersive VR (SMD: -0.62, 95%CI: -1.43 to 0.19, Z=1.51, P=0.132, I2:91.2%). Conclusion: It is suggested that health policymakers and managers equip burn wards with immersive VR devices to provide the basis for this intervention when caring for patients with burn wounds. Keywords: Virtual reality; burns; wound healing; pain; pain management; systematic review; meta-analysis Cite this article as: Norouzkhani N, Chaghian Arani R, Mehrabi H, Bagheri Toolaroud P, Ghorbani Vajargah P, Mollaei A, et al. Effect of Virtual Reality-Based Interventions on Pain During Wound Care in Burn Patients; a Systematic Review and Meta-Analysis. Arch Acad Emerg Med. 2022; 10(1): e84. https://doi.org/10.22037/aaem.v10i1.1756. ∗Corresponding Author: Mohammadreza Mobayen; Burn and Regener- ative Medicine Research Center, Guilan University of Medical Sciences, This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem N. Norouzkhani et al. 2 1. Introduction Based on the latest data from the World Health Organiza- tion, it is estimated that approximately 11 million people suf- fer severe burns that require medical care each year (1). Pa- tients with severe burns suffer irreversible physical and psy- chological consequences. They also undergo daily painful wound care procedures, including washing, debridement, and dressing changes (2). Proper burn wound management requires an accurate examination of the burn patient and ap- propriate treatment decisions (3-18). Patients describe burn pains as excruciating, sharp, tender, or aching during wound care, which causes the patient to remain quiet and not re- spond verbally or even complain of pain (19). Lack of ad- equate pain control impacts burn patients’ recovery nega- tively and is detrimental to the patient’s physical and mental health, confidence, and adherence to the treatment regimen. (20). Pharmacological intervention, such as use of opioid anal- gesics, is the first method of controlling pain in burn patients (21). Close monitoring of the intensity of pain, dose adjust- ment according to pain, and regular patient evaluation are necessary for the administration of opioids because of the different side effects and the possibility of physiological de- pendence or addiction (22). Therefore, in addition to pharmacotherapy, it is necessary to use cognitive and behavioural approaches, such as distrac- tion, reappraisal, information provision, relaxation training, and operant conditioning to reduce the need to use more opioids. Distraction can be used in various ways, such as through illustration, music, games, and attention tasks (23). Numerous theories have been proposed to explain how dis- traction affects the control or reduction of pain perception (24). Virtual reality (VR) is innovative, and one of the novel meth- ods used to distract patients from pain (25). VR technology, which can provide a comprehensive experience of the com- puter world, was originally built for gaming purposes but it now has expanded applicability in the health care industry and other sectors of the economy (26). Immersion in the virtual world allows patients to be distracted from painful procedures (27). Studies in the United States and Europe Rasht, Iran. Tel: +98-9125139506; +98-13-33552088; Email: moham- madreza.mobayen@yahoo.com, ORCID: https://orcid.org/0000-0001-9317- 4955. † Corresponding Author: Samad Karkhah; Nursing and Midwifery School of Shahid Dr Beheshti, Hamidyan Shahrak, Shahid Dr Beheshti Ave., Rasht, Guilan, Iran. Fax: +98-13-33550097; Postal code: 41469-39841, Tel: +98- 9032598167; +98-13-33552088; Email: sami.karkhah@yahoo.com, ORCID: https://orcid.org/0000-0001-9193-9176. have shown that combining VR therapy and analgesics sig- nificantly reduces pain perception (28-30). The availability of inexpensive VR technology has provided a good opportu- nity for its use in healthcare environments (23). It is impos- sible to consider technology’s advantages without consider- ing its disadvantages and side effects. Major disadvantages of VR include the need to teach the patient and provider how to use it, nausea, and motion sickness (31). Previous stud- ies on the effectiveness of VR technology for reducing the pain of burn patients have reported conflicting results. A study by Hoffman et al. (2019) showed that using of VR in- tervention significantly reduced the pain of burn wound de- bridement, while another study by Konstantatos et al. (2009) found that VR had no effect on reducing the pain intensity during dressing change on a burn patient (25, 32). Previ- ous systematic reviews and meta-analyses had some limita- tions. One meta-analysis evaluated the effect of VR on pain during burn wound care procedures and excluded cross-over and parallel study designs in the analysis. The overall effect was reported in six studies (33). Another meta-analysis re- ported the effect of fully immersive VR on pain experienced during dressing changes in hospitalized children and ado- lescents with severe burns based only on four studies (34). The present meta-analysis included parallel, cross-over or within-subjects studies on paediatric and adult populations to report the overall effect. Comprehensive sub-group and sensitivity analyses were also conducted in the present study. This study provides a systematic review and meta-analysis of VR-based interventions for pain control in burn patients dur- ing wound care. 2. Methods 2.1. Study registration and reporting This systematic review and meta-analysis was performed based on the Preferred Reporting Items for Systematic Re- views and Meta-Analysis (PRISMA) checklist (35). 2.2. Search strategy A comprehensive systematic search was conducted on in- ternational electronic databases such as Scopus, PubMed, Web of Science, and Iranian electronic databases such as Iranmedex, and Scientific Information Database (SID) with keywords extracted from Medical Subject Headings such as "Virtual reality", "Virtual reality therapy", "Virtual re- ality exposure therapy", "Virtual reality immersion ther- apy", "Exergaming”, “Active-video gaming”, “Burns”, “Wound healings”, “Pain”, and “Pain management” from the earli- est to May 6, 2022. For example, the search strategy in PubMed/MEDLINE database included search terms such as ((“Virtual reality”) OR (“Virtual realities”) OR (“Virtual reality therapy”) OR (“Virtual reality therapies”) OR (“Virtual real- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2022; 10(1): e84 ity exposure therapy”) OR (“Virtual reality immersion ther- apy”) OR (“Computer simulation”) OR (“Computer simula- tions”) OR (“Exergaming”) OR (“Multimedia”) OR (“Multi- medium”) OR (“Mobile applications”) OR (“Mobile apps”) OR (“Portable software apps”) OR (“Computer-assisted therapy”) OR (“Computer-assisted therapies”) OR (“Active-video gam- ing”)) AND ((“Wounds”) OR (“Wound healings”) OR (“Dress- ing change”)) AND ((“Pain”) OR (“Pain management”)) AND ((“Burns”) OR (“Burns patients”) OR (“Patients”) OR (“Clients”)). Keywords were combined with Boolean opera- tors "AND" and "OR". Persian keywords equivalent to the mentioned words were searched in Persian databases. Two researchers performed the search processes, separately. This review does not include gray literature such as expert opin- ions, conference presentations, dissertations, research and committee reports, and ongoing research. Gray literature in- cludes articles produced in print and electronic formats but not evaluated by a commercial publisher (36). 2.3. Inclusion and exclusion criteria In this review, randomized control trials (RCTs) that were published in English and Persian languages and utilized par- allel, cross-over or within-subjects designs focusing on the effect of different VR methods on pain of burn patients dur- ing burn wound care were included. Letters to the edi- tor, case reports, conference proceedings, qualitative studies, and reviews were excluded. 2.4. Study selection Data management was conducted using EndNote 8X soft- ware. Strategies included eliminating duplicate studies, eval- uating the title and abstract, and evaluating the full text of ar- ticles. The selection criteria of the studies were evaluated by two researchers, separately, based on the inclusion and ex- clusion criteria. Disagreements between the two researchers were examined and resolved by a third researcher. Finally, the resource list was evaluated manually to prevent data loss. 2.5. Data extraction and quality assessment The researchers extracted information from the studies used in this systematic review and meta-analysis, including first author’s name, year of publication, location, design, sam- ple size, type of intervention, duration of the study, dura- tion of intervention and follow-up, male/female ratio, age, type of control group, tool characteristics, specific Statisti- cal tests, and key results of studies. The Joanna Briggs In- stitute ( JBI) critical appraisal checklist was used to assess the quality of RCTs and quasi-experimental studies (37). JBI as- sesses the internal validity, the similarity of participants of compared groups, the reliability of outcomes measured, and the appropriateness of statistical analysis of RCT and quasi- experimental studies in 13 and 9 items, respectively. The quality of the studies in the systematic review and meta- analysis was evaluated by two researchers, separately, using a three-point reading range including "yes" (score 1), "no" (score 2), and "not applicable / not clear" (score 0). (38). The quality assessment levels of the studies in the JBI checklists were good (8), fair (6-7), and poor (5) (37). 2.6. Statistical analysis Data required for meta-analysis such as sample size of each intervention and control group, standard deviation (SD), study design (parallel, cross-over), type of intervention (im- mersive and non-immersive), risk of bias with JBI tool (good, fair, and poor), age group (paediatrics, adults, and both) of participants, and type of painful procedure (dressing, phys- iotherapy and debridement) were entered into Excel soft- ware. Data of studies that reported confidence interval, range, standard error and interquartile range (IQR) were con- verted to SD. To calculate the overall effect, the sample size, mean change and SD change were used in both intervention and control groups. The forest-plot chart reported the stan- dard mean difference (SMD) with the random-effect model (inverse-variance heterogeneity). A 95% confidence inter- val (CI) was used to determine the significance level (P- value<0.05). The overall negative effect was considered an indicator of the effectiveness of the VR intervention. Hetero- geneity was investigated with I2 value. I2 above 50% was con- sidered as substantial heterogeneity (39). Sub-group analysis based on study design, type of intervention, risk of bias based on JBI tool, age group of participants, and type of painful pro- cedure was performed. Publication bias was checked using the funnel plot, and then egger’s and Begg’s tests were used to measure the statistical significance. The trim and fill test was performed according to the significance of these two tests. Sensitivity analysis was performed to determine the depen- dence of "overall effect size" on each study included in the meta-analysis. 3. Results 3.1. Study selection A total of 3,936 studies were obtained through a comprehen- sive search of electronic databases. After removing duplicate articles, 3,180 articles remained. 2,856 studies were deleted after reviewing the title and abstract of the articles due to inconsistencies with the purpose of the present review. 226 studies were excluded due to their non-experimental design. After evaluating the full texts of 88 studies, thirty-eight were excluded due to issues in design. In addition, twenty studies were excluded due to a lack of required information. Finally, thirty studies (25, 28-30, 32, 40-64) were used in this system- atic review. Meta-analysis was performed on 23 RCTs with parallel, cross-over or within-subjects designs. The results of This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem N. Norouzkhani et al. 4 another seven quasi-RCTs were qualitatively reported (Figure 1). 3.2. Study characteristics A total of 1,293 patients with burns were included in 30 stud- ies (25, 28-30, 32, 40-64), and their mean age was 22.89 (SD=7.63) years. 70.72% of the participants were male, and 67.05% were in the intervention group. Twenty-three studies (25, 28, 30, 32, 41-50, 52-54, 56, 59, 60, 62-64) were RCTs with parallel, cross-over or within-subjects designs, while seven studies (29, 40, 51, 55, 57, 58, 61) had quasi-experimental designs. Of the studies in this systematic review and meta- analysis, twelve (25, 43, 47, 50-53, 55, 56, 59, 60, 62) reported the duration of the study with an average of 19.58 months. Eighteen studies (25, 28-30, 32, 41-44, 46-49, 52, 55, 58, 60, 63) reported duration of intervention with an average of 18.22 minutes. Of the studies in this systematic review and meta- analysis, thirteen (25, 30, 40, 42, 44, 46, 48, 49, 52, 56, 59, 62, 64) were conducted in the USA, and four (32, 41, 45, 50) in Australia, two (43, 51) in the Netherlands, two (54, 61) in Iran, two (28, 55) in Canada, two (57, 63) in Egypt, two (29, 58) in the UK, one (47) in South Africa, one (53) in China, and a study (60) in South Korea. Twenty-seven studies (25, 28-30, 32, 40-50, 52-54, 56, 57, 59-64) had a control group. Eleven studies (29, 40, 45, 50, 53, 54, 57, 58, 62-64) used VAS (Visual analog scale), nine (25, 30, 42, 44, 46, 48, 49, 59, 61) studies GRS (Graph rating scale), and seven (28, 45, 50, 53, 55, 57, 62) studies utilized FLACC (Faces, legs, activity, cry and consola- bility) to measure pain in participants (Table 1). 3.3. Methodological quality assessment of eligi- ble studies Of the thirty studies (25, 28-30, 32, 40-64), twenty (25, 28, 29, 32, 40, 42, 43, 45, 47, 50, 52-54, 57, 59-64) had good quality, while ten studies (30, 41, 44, 46, 48, 49, 51, 55, 56, 58) had fair quality (Figures 2 & 3). 3.4. Effect of VR methods on pain of burn pa- tients during wound care Thirty studies (25, 28-30, 32, 40-64) in the present systematic review examined the effect of different VR methods on reduc- ing pain during wound care in burn patients. The charac- teristics of the interventions in the included studies are pre- sented in Table 2. Overall, the results of twenty-two stud- ies (25, 28-30, 40-46, 48, 49, 51, 53, 57-60, 62-64) showed that different VR methods reduced pain, while one study (32) showed that it increased pain when caring for burn wounds. However, the results of seven studies (47, 50, 52, 54-56, 61) showed that different VR methods did not affect patients’ pain when caring for burn wounds. 3.5. A meta-analysis of the effect of different VR methods on reducing pain during wound care in burn patients The result of the meta-analysis demonstrated that the use of VR intervention, compared to the control group, led to a sig- nificant reduction in pain intensity (SMD: -0.70, 95%CI: -0.97 to -0.43, Z=5.05, P<0.001, I2:82.0%) (Figure 4). The results of the subgroup analysis showed that immersive VR intervention significantly reduces pain intensity (SMD: - 0.73, 95%CI: -0.97 to -0.49, Z=5.88, P<0.001, I2:69.3%). How- ever, non-immersive VR intervention did not show a statisti- cally significant effect on pain intensity (SMD: -0.62, 95%CI: -1.43 to 0.19, Z=1.51, P=0.132, I2:91.2%) (Figure 4). The sub-group analyses showed that the included studies with different levels of bias (good and fair) significantly re- duced pain intensity in the VR intervention groups. Other results from sub-group analysis showed that VR interven- tion had significant effects on pediatrics and both age groups (pediatrics and adults); however, it was not statically signif- icant in the adults. Also, sub-group analysis indicated that VR intervention significantly reduced pain intensity in differ- ent burn procedures, such as dressing changes, wound de- bridement, and physical therapy. Studies with parallel and cross-over designs showed that VR significantly affected in- tervention groups (Table 3). Sensitivity analysis showed that the overall effect of VR on pain severity levels did not depend on a single study (95%CI: -1.03 to -0.35). Based on the visual inspection of the funnel plot, we found an asymmetry (Figure 5). We did not observe any change in the overall effect size (SMD: -0.62, 95%CI: -0.88 to -36). Begg’s (P=0.02) and Egger’s regression tests (P=0.04) indicated a sig- nificant publication bias. Therefore, meta-trim with fill-and- trim method was used to correct probable publication bias. 4. Discussion In the present systematic review, the effects of various VR methods were evaluated on patients’ pain when undergoing care for burn wounds. Findings delineated that twenty-two interventions reduced pain and one intervention increased pain. Meanwhile, seven interventions did not affect patients’ pain. A meta-analysis was performed on 23 studies with par- allel and cross-over RCT designs, which showed that VR in- tervention significantly reduced pain intensity. One of the most important outcomes for burn patients is pain relief when caring for burn wounds. Pain in these pa- tients is due to hypersensitivity of the pain pathways in the central and peripheral nervous systems (65). Lack of proper pain management can provoke a reaction and arousal in the later stages of burn wound care (66-78). Therefore, proper pain management is particularly important in these patients. In recent years, non-pharmacological approaches to reliev- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 5 Archives of Academic Emergency Medicine. 2022; 10(1): e84 ing pain in burn patients have been considered. One of these approaches is VR, which has rare side effects (62). In the present review, various VR methods were used in addi- tion to conventional therapies to reduce pain during wound care in burn patients. A systematic review and meta-analysis was performed by Chan et al. on the clinical efficacy of VR in managing acute pain in various procedures. The Chan et al. study showed that VR could effectively relieve procedural pain, but its statistical analyses had issues with heterogene- ity (79). Another review study examined the effect of VR in- terventions on procedural pain in paediatrics, which showed that VR interventions reduced pain in children more than standard care (80). A narrative review study examined the ef- fect of VR on acute and chronic pain in adult patients. One of the topics studied in this study was the effect of VR on pain when changing dressings. This study showed that in 12 out of the eighteen studies reviewed, VR significantly reduced pain (81). Another review examined VR as a pain management tool and demonstrated that VR therapy could be suitable for distracting the patient while creating painful stimuli (82). An- other systematic review and meta-analysis study examined the effect of VR on acute and chronic pain in adults. The re- sults showed that VR effectively reduced acute pain in these patients. However, some studies have shown that VR can also reduces chronic pain, so more research is needed on the ef- fect of VR on reducing chronic pain (83). Another systematic review also examined the effect of interactive VR on pain per- ception in patients, which showed that this intervention ef- fectively reduced pain. However, more intervention studies are needed to confirm the effectiveness of VR intervention in reducing pain (84). Results of a meta-analysis based on 23 studies with parallel and cross-over RCTs design showed that VR intervention sig- nificantly reduced pain intensity. The results of the present study were consistent with the results of previous meta- analyses. One meta-analysis (2022) was performed with six studies to evaluate the effects of VR on pain intensity and other outcomes. Sub-group analysis results of this particu- lar study showed that immersive VR (4 studies) significantly decreased pain intensity, and non-immersive VR (2 studies) had no effect on patients’ pain perception (33). Based on the results of the current meta-analysis, immersive VR interven- tion (18 studies) significantly decreased pain intensity in the intervention group. However, non-immersive VR (7 studies) did not cause a statistically significant difference between intervention and control groups. In the non-immersive VR technique, the least interactive activities, such as interaction with the keyboards and mice without fully immersing into the environment, occurred. In immersive VR, the interaction is the highest and subjects are fully immersed in and inter- act with the VR environment (85). The current meta-analysis showed that VR intervention had a statistically significant ef- fect on pediatric patients; however, it was ineffective among the adult age group. Various factors, such as different contex- tual factors in pain perception in each age group and mea- surement scales, can affect pain intensity. Also, one meta- analysis on paediatrics revealed that immersive VR signifi- cantly decreased pain intensity (34). Future studies should compare VR effects on adults and paediatrics. The present systematic review results showed that out of thirty VR interventions, twenty-two interventions reduced patients’ pain during burn wound care procedures. The meta-analysis found that VR can statistically decrease pain intensity in the intervention group compared to the control group. According to the results of previous studies and the present systematic review and meta-analysis, it is suggested that health policymakers and managers consider equipping burn wards/units with VR devices to provide the basis for this intervention when caring for burn patients. To compare the effects of VR intervention among different age groups and immersive vs non-immersive VR, it is recommended that fu- ture research be focused on this area. 5. Limitations There are limitations in this study that are noteworthy. This systematic review and meta-analysis is based on the PRISMA checklist but is not listed in the international prospective register of systematic reviews database (PROSPERO). Al- though two researchers completed the search of electronic databases, all studies on this subject may not have been found. Finally, only studies in English and Persian have been included, and studies in other languages have not been in- cluded. 6. Implications for health managers and policymakers Considering the importance of pain management when car- ing for burn patients using various interventions, including VR methods, and also considering the results of this system- atic review and meta-analysis, it is suggested that health pol- icymakers and managers equip burn wards with VR devices to provide the basis for this intervention when caring for the wounds of these patients, as well as develop policies and guidelines regarding the use and deployment of VR technol- ogy in the management of pain in burn patients. 7. Implications for future research In the results of this meta-analysis study, studies that applied the immersive VR or performed on pediatric patients showed a more significant effect on the intervention than the control group. However, studies that applied non-immersive VR or included adults; demonstrated no significant difference be- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem N. Norouzkhani et al. 6 tween intervention and control groups. Therefore, it is sug- gested that future studies focus on comparing immersive and non-immersive VR interventions in paediatrics with adults. 8. Conclusion In the present systematic review, the effects of various VR methods were evaluated on patients’ pain when undergoing care for burn wounds, which showed that immersive VR in- tervention significantly decreased pain intensity in the inter- vention group. Health policymakers and managers should equip burn wards with immersive VR devices to provide the basis for this intervention when caring for these patients’ wounds. 9. Declarations 9.1. Acknowledgments None. 9.2. Authors’ contributions Study concept and design by all authors; Data acquisition by all authors; Data interpretation by all authors; drafting of the manuscript by all authors; Revision of the manuscript by all authors; the final version of the manuscript is approved by all authors. 9.3. Data availability The datasets generated and analyzed during the current study are available from the corresponding author upon rea- sonable request. 9.4. Funding None. 9.5. Competing interests The authors declare no conflict of interest. References 1. WHO. Burns [Internet]. World Health Organi- zation; 2018 [updated 2018 March 6. Available from: https://www.who.int/en/news-room/fact- sheets/detail/burns. 2. Scheffler M, Koranyi S, Meissner W, Strauss B, Rosendahl J. Efficacy of non-pharmacological interventions for pro- cedural pain relief in adults undergoing burn wound care: A systematic review and meta-analysis of random- ized controlled trials. Burns. 2018;44(7):1709-20. 3. 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The effect of interactive virtual reality on pain percep- tion: a systematic review of clinical studies. Disabil Re- habil. 2020;42(26):3722-33. 85. Shahrbanian S, Ma X, Aghaei N, N K-B, Simmonds M. Use of virtual reality (immersive vs. non immersive) for pain management in children and adults: A systematic review of evidence from randomized controlled trials. Euro J Exp Bio. 2012;2:1408-22. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem N. Norouzkhani et al. 10 Figure 1: Flow diagram of the study selection process. Figure 2: Methodological quality assessment of RCT studies using Joanna Briggs Institute ( JBI) checklist. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 11 Archives of Academic Emergency Medicine. 2022; 10(1): e84 Figure 3: Methodological quality assessment of quasi-experimental studies using Joanna Briggs Institute ( JBI) checklist. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem N. Norouzkhani et al. 12 Figure 4: Sub-group analysis based on immersive and non-immersive VR intervention. SMD: standard mean difference; CI: confidence inter- val. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 13 Archives of Academic Emergency Medicine. 2022; 10(1): e84 Figure 5: Funnel plot for asymmetry evaluation in included studies. SMD: standard mean difference. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem N. Norouzkhani et al. 14 Table 1: Basic characteristics of the studies included in this systematic review and meta-analysis First Au- thor/year Location Study characteristics 1. Design 2. Sample Size (I/C) 3. Intervention 4. Duration of study 5. Duration of intervention 6. Duration of follow-up M/F ratio (%) Age (mean±SD) Control group Tool characteristics 1. Name of the questionnaire 2. Number of items 3. Overall scoring of items Interven- tion type Key results JBI Score Hoffman et al., 2001 (40) USA 1. Quasi- experimental 2. 7 3. VR 4. N/A 5. N/A 6. 3 days 85.71/14.29 21.90 All participants served as their own control when had not received VR distraction. 1. VAS 2. 100 3. 0 to 100 Immersive The mean score of pain in participants was decreased during the intervention in the intervention group compared to the control group (P< 0.010). Good Das et al., 2005 (41) Australia 1. RCT (Crossover) 2. 7 3. VR 4. N/A 5. 27.5 minutes 6. 0 N/A 11.10 (SD=3.50) All participants served as their own control when had not received VR. 1. Face scale 2. 10 3. 0 to 10 Immersive The mean score of pain in patients was decreased after the intervention in the intervention group compared to the control group (P<0.01). Fair Sharar et al., 2007 (42) USA 1. RCT 2. 234 (88/146) 3. VR 4. N/A 5. 15 minutes 6. 0 82.91/17.09 N/A Participants in the control group had not received VR. 1. GRS 2. 100 mm 3. 0 to 100 Immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P<0.05). Good van Twillert et al., 2007 (43) Netherl- and 1. RCT 2. 19 3. VR 4. 13 months 5. 19.2 minutes 6. 2 days 63.16/36.84 30.00 All participants served as their own control when had not received VR. 1. VAT 2. 100 mm 3. 0 to 100 Immersive The mean score of pain in participants was decreased during and a day after the intervention in the intervention group compared to the control group (P<0.05). Good Hoffman et al., 2008 (44) USA 1. RCT (Crossover) 2. 11 3. VR 4. N/A 5. 3 minutes 6. N/A 100/0 27.00 All participants served as their own control when had not received VR. 1. GRS 2. 10 cm 3. 0 to 10 Immersive The mean score of pain in patients was decreased during the intervention in the intervention group compared to the control group (P=0.015). Fair Mott et al., 2008 (45) Australia 1. RCT 2. 42 (20/22) 3. AR 4. N/A 5. N/A 6. 0 69.05/30.95 N/A Participants in the control group had not received the AR. 1. FLACC pain assessment tool 2. 5 items 3. 0 to 10 1. FPS-R 2. N/A 3. N/A 1. VAS 2. 5 cm 3. 0 to 5 Non- immersive The mean score of pain in participants (long dressing times) was decreased during the intervention in the intervention group compared to the control group (P=0.006). Good This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 15 Archives of Academic Emergency Medicine. 2022; 10(1): e84 Table 1: Basic characteristics of the studies included in this systematic review and meta-analysis Carrougher et al., 2009 (46) USA 1. RCT (Crossover) 2. 39 3. VR 4. N/A 5. 10 minutes 6. 0 89.74/10.26 35.00 (SD=11.00) Participants in the control group had not received VR. 1. GRS 2.100 mm 3.0 to 100 Immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P=0.004). Fair Konstan- tatos et al., 2009 (32) Australia 1. RCT 2. 86 (43/43) 3. VR 4. N/A 5. 18 minutes 6. 0 N/A 38.60 (SD=15.95) Participants in the control group had not received VR. 1. BSAR 2.10 cm 3.0 to 10 Non- Immersive The mean score of pain in participants was increased during and after the intervention in the intervention group compared to the control group (P<0.05). Good Morris et al., 2010 (47) South Africa 1. RCT (Crossover) 2. 11 3. VR 4. 4 months 5. 18 minutes 6. 0 N/A N/A All participants served as their own control when had not received VR. 1.NPRS 2.N/A 3.N/A 1.BSPAS 2.100 mm 3.0 to 100 Non- immersive There was no significant difference in pain scores during the intervention between the intervention and control groups (P=0.13). Good Maani et al., 2011 (48) USA 1. RCT (Crossover) 2. 12 3. VR 4. N/A 5. 12 minutes 6. 0 100/0 N/A All participants served as their own control when had not received VR. 1. GRS 2.100 mm 3.0 to 100 Immersive The mean score of pain in participants was decreased during the intervention in the intervention group compared to the control group (P<0.05). Fair Schmitt et al., 2011 (49) USA 1. RCT (Crossover) 2. 54 3. VR 4. N/A 5. 6.5 minutes 6. 0 81.48/18.52 12.00 (SD= 3.90) All participants served as their own control when had not received VR. 1. GRS 2.100 mm 3.0 to 100 Immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P< 0.05). Fair Kipping et al., 2012 (50) Australia 1. RCT 2. 41 (20/21) 3. VR 4. 15 months 5. N/A 6. 0 68.29/31.71 13.05 (SD=1.55) Participants in the control group had not received the VR. 1. FLACC pain assessment tool 2.5 items 3. 0 to 10 1. VAS 2.10 cm 3. 0 to 10 Immersive There was no significant difference between the intervention and the control group in pain score during dressing removal and application (P>0.05). Good Faber et al., 2013 (51) Netherlands 1. Quasi- experimental 2. 36 3. VR 4. 40 months 5. N/A 6. 7 days 83.33/16.67 27.70 (SD=15.20) N/A 1. VAT 2.10 cm 3.0 to 10 Immersive The mean score of pain in participants was decreased during the intervention on days one, two, and three (P< 0.05). Fair Jeffs et al., 2014 (52) USA 1. RCT 2. 28 (18/10) 3. VR 4. 22 months 5. 52.5 minutes 6. 0 32.14/67.86 13.50 (SD=2.30) Participants in the control group had not received the VR. 1.APPT 2.115 mm 3.0 to 115 Immersive There was no significant difference in pain scores between the intervention and control groups during the intervention (P=0.32). Good This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem N. Norouzkhani et al. 16 Table 1: Basic characteristics of the studies included in this systematic review and meta-analysis Hua et al., 2015 (53) China 1. RCT 2. 65 (33/32) 3. VR 4. 12 months 5. N/A 6. 0 47.69/52.31 8.72 (SD=3.38) Participants in the control group had not perceived the VR. 1. Faces picture scale 2.10 items 3.0 to 10 1. FLACC pain assessment tool 2.5 items 3. 0 to 10 1. VAS 2.10 cm 3. 0 to 10 Immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P<0.05). Good Ebrahimi et al., 2017 (54) Iran 1. RCT 2. 60 (40/20) 3. VR 4. N/A 5. N/A 6. 5 days 56.67/43.33 35.00 (SD=10.00) Participants in the control group had not received the VR. 1. VAS 2.10 cm 3.0 to 10 Non- immersive There was no significant difference in pain scores before and after the intervention between intervention and control groups from day one to five (P>0.05). Good Khadra et al., 2018 (55) Canada 1. Quasi- experimental 2. 15 3. VR 4. 7 months 5. 18.4 minutes 6. 0 40.00/60.00 2.20 (SD=2.10) N/A 1. FLACC pain assessment tool 2.5 items 3. 0 to 10 Non- immersive There was no significant difference in pain scores before and after the intervention in the intervention group (P>0.05). Fair McSherry et al., 2018 (56) USA 1. RCT (Crossover) 2. 18 3. VR 4. 29 months 5. N/A 6. 0 72.22/27.78 38.40 (SD=15.50) All participants served as their own control when had not received VR. 1. VNS 2.10 cm 3.0 to 10 Immersive There was no significant difference in pain intensity between intervention and control groups after intervention (P>0.05). Fair Soltani et al., 2018 (30) USA 1. RCT (Crossover) 2. 39 3. VR 4. N/A 5. 6 minutes 6. 0 N/A 36.00 All participants served as their own control when performing ROM exercises without VR distraction. 1. GRS 2.100 mm 3.0 to 100 Immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P< 0.005). Fair Fatma & Ghada, 2019 (57) Egypt 1. Quasi- experimental 2. 60 (30/30) 3. VR 4. N/A 5. N/A 6. 0 60.00/40.00 N/A Participants in the control group had not received VR. 1. Faces picture scale 2.10 items 3.0 to 10 1. FLACC pain assessment tool 2.5 items 3. 0 to 10 1. VAS 2.10 cm 3. 0 to 10 Immersive The mean score of pain in participants was decreased during and after the intervention in the intervention group compared to the control group (P<0.001). Good Hoffman et al., 2019 (25) USA 1. RCT 2. 48 3. VR 4. 35 months 5. 5 minutes 6. N/A 70.83/29.17 12.00 All participants served as their own control when had not received VR. 1. GRS 2.10 cm 3.0 to 10 Immersive The mean score of pain in participants was decreased during the intervention in the intervention group compared to the control group (P<0.001). Good This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 17 Archives of Academic Emergency Medicine. 2022; 10(1): e84 Table 1: Basic characteristics of the studies included in this systematic review and meta-analysis Phelan et al., 2019 (58) UK 1. Quasi- experimental 2. 15 3. VR 4. N/A 5. 5 minutes 6. 0 66.67/33.33 25.00 N/A 1. VAS 2.100 3.0 to 100 Immersive and non- immersive • The pain threshold time was increased after the intervention in participants (P=0.003). • The pain tolerance time was increased after intervention in participants (P<0.001). • The pain tolerance time was significantly different between VR scenarios in participants (P<0.05). • The mean score of maximum pain in participants was significantly different in VR scenarios (P=0.002). Fair Hoffman et al., 2020 (59) USA 1. RCT 2. 50 3. VR 4. 29 months 5. N/A 6. 10 days 84.00/16.00 N/A Participants in the control group had not received VR. 1. GRS 2.10 cm 3. 0 to 10 Immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P<0.05). Good Joo et al., 2020 (60) South Korea 1. RCT 2. 57 (28/29) 3. VR 4. 4 months 5. 30 minutes 6. 0 94.74/5.26 44.88 (SD=11.09) Participants in the control group had not received VR. 1. MHQ 2. N/A 3.0 to 100 Immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P=0.002). Good Khadra et al., 2020 (28) Canada 1. RCT 2. 38 3. VR 4. N/A 5. 25 minutes 6. 0 71.05/28.95 1.82 (SD=1.32) All participants served as their own control when had not received VR. 1. FLACC 2.5 items 3.0 to 10 1. NRS-obs 2.N/A 3.N/A Non- immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P<0.05). Good Kiani et al., 2020 (61) Iran 1. Quasi- experimental 2. 45 (30/15) 3. VR 4. N/A 5. N/A 6. 0 N/A 31.38 (SD=8.47) Participants in the control group had not received VR. 1. GRS 2.100 mm 3.0 to 100 1.BSPAS 2.100 mm 3.0 to 100 Immersive There was no significant difference in pain intensity between intervention and control groups during the intervention (P>0.05). Good Phelan et al., 2021 (29) UK 1. Quasi- experimental 2. 20 (15/5) 3. VR 4. N/A 5. 36.9 minutes 6. 0 60.00/40.00 48.20 (SD= 19.68) Participants in the control group had not received the VR. 1. VAS 2.100 mm 3.0 to 100 Immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P= 0.007). Good This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem N. Norouzkhani et al. 18 Table 1: Basic characteristics of the studies included in this systematic review and meta-analysis Xiang et al., 2021 (62) USA 1. RCT 2. 90 (61/29) 3. VR 4. 25 months 5. N/A 6. 0 50.00/50.00 11.30 Participants in the control group had not received the VR. 1. VAS 2.100 3.0 to 100 1. FLACC 2.5 items 3.0 to 10 Immersive and non- immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P<0.05). Good Ali et al., 2022 (63) Egypt 1. RCT 2. 22 (11/11) 3. VR 4. N/A 5. 20 minutes 6. 0 59.09/40.91 13.18 (SD=1.73) Participants in the control group had not received the VR. 1. VAS 2.10 cm 3.0 to 10 Immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P<0.001). Good Armstro- ng et al., 2022 (64) USA 1. RCT 2. 24 (11/13) 3. VR 4. N/A 5. N/A 6. 7 days 79.17/20.83 11.50 (SD=3.10) Participants in the control group had not received the VR. 1. VAS 2.10 cm 3.0 to 10 Non- immersive The mean score of pain in participants was decreased after the intervention in the intervention group compared to the control group (P<0.05). Good RCT: Randomized clinical trial; ANOVA: Analysis of variance; VAS: Visual analog scale; VR: Virtual reality; AR: Augmented reality; FLACC: Faces, legs, activity, cry and consolability; FPS-R: Faces pain scale-revised; GRS: Graph rating scale; VR- PAT: Virtual reality pain alleviation tool; BSAR: Burns specific anxiety rating; VNS: Verbal numeric scale; MHQ: Michigan hand outcomes questionnaire; BSPAS: Burn specific pain anxiety scale; APPT: Adolescent pediatric pain tool; NPRS: Numeric pain rating scale; VAT: Visual analog thermometer; NRS-obs: Numeric Rating Scale-observational; N/A: not applicable; SD: standard deviation; JBI: Joanna Briggs Institute; ROM: Range of motion. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 19 Archives of Academic Emergency Medicine. 2022; 10(1): e84 Table 2: Interventions of the studies included in the systematic review and meta-analysis First Au- thor/year Intervention Program Description Hoffman et al., 2001 (40) VR Participants received VR distraction. The intervention was as follows: Patients underwent active-assisted physical therapy exercises with a VR helmet. A motion-sensing system was used with a VR helmet to measure the position of the participant’s head. The first participant was placed in the virtual environment of the Spider World where she/he could move virtual objects with her/his cyber hands. Other participants were placed in the Snow World where they could move and throw snowballs. the pain was measured via VAS during the intervention. Das et al., 2005 (41) VR Participants received 10 to 45 minutes of VR. The intervention was as follows: Coin toss was used to sequence the analgesic test using medication or using medication and VR. The content in VR was a game based on the age group of the participants. Participants could shoot monsters using a pointer. The game was designed so that participants could play with minimal movement during dressing changes. The pain was measured via the face scale immediately after the intervention. Sharar et al., 2007 (42) VR Participants received immersive VR distraction for 15 minutes during physical therapy. The VR intervention was such that using a large screen above the patient’s head with sound effects and moving explosions of blue, white, and green, the patient’s communication with the environment was blocked. The Snow World content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. The pain was measured via the GRS immediately after the intervention. van Twillert et al., 2007 (43) VR Participants received 19.2 minutes of VR during wound dressing change. VR intervention consisted of a pair of 3D glasses and an integrated audio system. The Snow World content included a snowy environment in which participants threw snowballs at snowmen, igloos, and penguins using the keys on the mouse and keyboard. There were special effects such as river and sky along with sound effects in this intervention. The pain was measured via the VAT one day before, during, and after wound dressing. Hoffman et al., 2008 (44) VR Participants received 3 minutes of VR distraction. The intervention was as follows: Patients underwent wound debridement for three minutes with a VR waterproof cap. In Immersive VR intervention, helmets, headphones, and joysticks were used to control the movement of snowballs and their launch. The Snow World content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. The pain was measured via GRS during the intervention. Mott et al., 2008 (45) AR Participants received AR during dressing change. AR is a device that has several sculptures on top of it and is lifted by a camera, creating a three-dimensional character called Hospital Harry. A voice or the child’s parents encouraged the child to continue and change the animation. By manipulating the camera, the child can visualize the existing character from different angles. The pain was measured via the FLACC pain assessment tool, the FPS-R, and the VAS before, during, and after the intervention. Carrougher et al., 2009 (46) VR Participants received VR during physical therapy for 10 minutes. VR intervention consisted of a pair of 3D glasses and an integrated audio system. The Snow World content included a snowy environment in which participants threw snowballs at snowmen, igloos, and penguins using the keys on the mouse and keyboard. There were special effects such as river and sky along with sound effects in this intervention. The pain was measured via GRS immediately after the intervention. Konstantatos et al., 2009 (32) VR Participants received VR relaxation with intravenous morphine patient-controlled analgesia during dressing change. VR relaxation intervention includes VR glasses, a headset, a DVD player, and a relaxing DVD. The content of the DVD includes the sequence "Snow World", which is based on the theory of hypnotherapy. The program includes videos of soothing scenery that end with a spiral, and participants are asked to focus on the spiral. The pain was measured via the BSAR before, during, and after the intervention. Morris et al., 2010 (47) VR Participants received a low-cost VR system with analgesia during physiotherapy for 18 minutes. The order of the meetings was determined using a coin toss. Low-cost VR system intervention used a VR display on the patient’s head and contained a game called "Walt Disney’s Chicken Little". The pain was measured via the BSPAS, and NPRS by a blinded assessor during physiotherapy. Maani et al., 2011 (48) VR Participants received robot-like arm-mounted VR goggles during wound care for 12 minutes. A random number generator was used to determine the order of intervention. The VR intervention consisted of a VR glass, a spectacle holding system, and a custom robot-like arm. The Snow World content included a snowy environment in which participants threw snowballs at snowmen, igloos, and penguins using the keys on the arm. There were special effects such as river and sky along with sound effects in this intervention. The pain was measured via the GRS during wound care. Schmitt et al., 2011 (49) VR Participants received 3-10 minutes of VR distraction during physical therapy. The intervention was as follows: Patients underwent post-burn physical therapy with a VR helmet. A motion-sensing system was used with a VR helmet to measure the position of the participant’s head. The participants were placed in the virtual environment of the Snow World where they could move and throw snowballs. The Snow World content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. The pain was measured via GRS immediately after the intervention. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem N. Norouzkhani et al. 20 Table 2: Interventions of the studies included in the systematic review and meta-analysis First Au- thor/year Intervention Program Description Kipping et al., 2012 (50) VR Participants received an Off-the-shelf VR system during dressing removal and application. The intervention was performed using a VR display on the head with a tracker and manual joystick control. The VR content displayed for patients was “Chicken Little” and “Need for Speed” games. The pain was measured via the FLACC pain assessment tool and the VAS before and during the intervention. Faber et al., 2013 (51) VR Participants received VR distraction in daily wound care. The intervention was as follows: Patients underwent wound care with a VR helmet. Motion-sensing system and integrated audio system were used with a VR helmet to place participants in the virtual environment of the Snow World where they could move and throw snowballs. The Snow World content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. The pain was measured via VAT during and after interventions. Jeffs et al., 2014 (52) VR Participants received VR distraction during burn wound care. VR distraction intervention was performed using a VR helmet, a tripod with a hinged arm, headphones, and interaction with a trackball. The VR content of the game was Snow World. The Snow World content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. The pain was measured via the VAS during the intervention. Hua et al., 2015 (53) VR Participants received VR distractions during dressing changes. VR distractions intervention was performed using a VR headset and headphones. The content of VR distraction was a third-person game called Ice Age 2: The Meltdown, in which participants control the game character in a snowy environment to reach the oak. The pain was measured via the FLACC pain assessment tool, the faces picture scale, and the VAS before, during, and after the intervention. Ebrahimi et al., 2017 (54) VR Participants received VR for five days during dressing changes. The VR intervention was performed with a VR goggle and headset through which audio and video were streamed. The pain was measured via the VAS. Khadra et al., 2018 (55) VR Participants received a VR dome environment during hydrotherapy for a mean of 18.4 minutes. The VR dome intervention consists of a curved plate located at the end of the hydrotherapy reservoir. The content of this intervention includes a game called bubbles in which there is a mouse and the child presses it to produce bubbles. Also, animals appear on the screen, which produce funny sounds and emoticons and the child is inside a wagon that passes between/through them. The pain was measured via the FLACC pain assessment tool, one hour before, immediately before, 10 minutes after onset, immediately after, and 30 minutes after hydrotherapy. McSherry et al., 2018 (56) VR Participants received immersive VR during dressing changes. The VR intervention was such that using a large screen above the patient’s head with sound effects and moving explosions of blue, white, and green, the patient’s communication with the environment was blocked. The Snow World content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. The pain was measured via the VNS before and after the intervention. Soltani et al., 2018 (30) VR Participants received 3 minutes of VR distraction. The intervention was as follows: Patients underwent active physical therapy exercises with VR goggles. Participants were randomly divided into two groups with/without VR treatment orders. The participants were placed in the virtual environment of the Snow World where they could move and throw snowballs. The Snow World content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. The pain was measured via GRS immediately after the intervention. Fatma & Ghada, 2019 (57) VR Participants received VR technology during dressing change. VR technology intervention involves a mobile phone with a 3D animation that sits on a device with 3D glasses on the head that also has headphones. The pain was measured via the FLACC pain assessment tool, the faces picture scale, and the VAS before, during, and after the intervention. Hoffman et al., 2019 (25) VR Participants received 5 minutes of VR distraction during wound cleaning. The intervention was as follows: Patients underwent wound care with waterproof VR goggles that were fixed near their eyes. Participants were randomly divided into two groups with/without VR treatment orders. The participants explored the virtual environment of the Snow World, with a mouse, where they could move and throw snowballs. The Snow World content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. The pain was measured via GRS during the intervention. Phelan et al., 2019 (58) VR Participants received four different VR scenarios, each lasting an average of 5 minutes. The four VR scenarios were as follows: • Henry scenario: A passive scenario based on a hedgehog’s birthday party. • Flocker: An active scenario in which the participant is tasked with collecting sheep using special obstacles. • Blindness: It was a passive scenario based on the story of a blind person. • Basket: It was an active scenario in which the participant received a variety of feedback based on entering the ball into the basketball hoop. Pain experienced by participants was measured using a cold compressor test that included a 4 °C cold water tank. The pain was measured via the VAS. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 21 Archives of Academic Emergency Medicine. 2022; 10(1): e84 Table 2: Interventions of the studies included in the systematic review and meta-analysis First Au- thor/year Intervention Program Description Hoffman et al., 2020 (59) VR Participants received VR distraction during wound debridement. The intervention was as follows: Patients underwent wound care with waterproof VR goggles that were fixed near their eyes. The participants explored the virtual environment of the Snow World, with a mouse, where they could move and throw snowballs. The Snow World content was such that patients threw snowballs at snowmen, igloos, robots, and penguins at the push of a button. The pain was measured via GRS after the intervention. Joo et al., 2020 (60) VR Participants received VR-based rehabilitation for 30 minutes. The intervention involved using a system called RAPAEL Smart Glove, which was a combination of a glove and a VR system. This system collects the patient’s active movements with gloves. The training program in using this glove included the following: • Pronation and supination of the forearm • Bending and stretching of the wrist • Radial deviation and ulnar of the wrist • Bending and stretching of the fingers Patient pain was measured via using visual and auditory feedback and also measured based on MHQ using a squeeze dynamometer. Khadra et al., 2020 (28) VR Participants received 10 minutes of VR distraction during hydrotherapy. The intervention was as follows: Patients underwent wound care in the hydrotherapy tank with projector-based hybrid VR. Participants were randomly divided into two groups with/without VR treatment orders. The participants played the Bubbles video game with a mouse or automatic mode. Patient pain was measured via FLACC scale and NRS at the following times: T1: before the intervention, T2: first 5 minutes of intervention, T3: end of the first phase of wound care session, T4: end of the second phase of wound care session, and T5: 30 minutes after end of wound care session. Kiani et al., 2020 (61) VR Participants received VR. The VR intervention consisted of VR glasses with a helmet that had two speakers inside the helmet to hear the sound, as well as gloves with a sensor. To detect the movement of the head, there was a tracker sensor inside the helmet that signaled the participants’ movements to the computer. The content of this intervention included a game that had a cold and snowy atmosphere and the user threw snowballs at the snowmen to get points. The pain was measured via the GRS and BSPAS before and after the intervention. Phelan et al., 2021 (29) Participants received four different VR scenarios. In this intervention, an Oculus Rift VR display system on the patient’s head, a remote control, and a head tracker were used to monitor and detect movement. The four different VR scenarios were as follows: • Birthday celebration of a hedgehog • Documentary on visual impairments • Puzzle-based experience • Basketball experience Xiang et al., 2021 (62) VR Participants received two types of VR-PAT. The intervention was performed using an iPhone and headphones. Two types of VR-PAT were as follows: • Active VR-PAT: The content of this intervention includes a game called Virtual River cruise. The game involved guiding a boat to shore, with snow sculptures in the middle of the road where the participants could guide the boat by shaking their head and receiving the sculptures. • Passive VR-PAT: The content of this intervention is the same as the active intervention, but the participants do not interact in it. The pain was measured via the FLACC pain assessment tool and the VAS. Ali et al., 2022 (63) VR Participants received VR Oculus with physical therapy seasons, each season lasting for 20 minutes. VR oculus uses a VR goggle to restrict children’s vision of the hospital environment. Children can choose their favorite video from the beginning of the intervention. In addition to VR glasses, headphones are also provided to play audio. The pain was measured via the VAS before and after the intervention. Armstrong et al., 2022 (64) VR Participants received VR-PAT for 7 days during the dressing change. The VR-PAT intervention includes a VR headset with a virtual river cruise game that runs on smartphones. The game involved guiding a boat to shore, with snow sculptures in the middle of the road where the participant could guide the boat by shaking its head and receiving the sculptures. The pain was measured via the APPT. VR: Virtual reality; VAS: Visual analog scale; GRS: Graph rating scale; VAT: Visual analog thermometer; Augmented reality; FLACC: Faces, legs, activity, cry and consolability; FPS-R: Faces pain scale-revised; BSAR: Burns specific anxiety rating; BSPAS: Burn specific pain anxiety scale; NPRS: Numeric pain rating scale; VNS: Verbal numeric scale; MHQ: Michigan hand outcomes questionnaire; NRS: Numeric Rating Scale; VR-PAT: Virtual reality pain alleviation tool; APPT: Adolescent pediatric pain tool. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem N. Norouzkhani et al. 22 Table 3: Sub-group analysis of included studies Sub-categories Number* Effect size** 95%CI Z P I2 Bias Good 19 -0.69 -1.03 to -0.35 3.97 <0.001 85.4% Fair 6 -0.74 -1.06 to -0.43 4.59 <0.001 37.5% Age group Pediatric 14 -0.81 -1.22 to -0.39 3.83 <0.001 82.9% Adult 7 -0.45 -1.01 to 0.10 1.59 0.11 84.0% Both 4 -0.53 -0.81 to -0.26 3.0 0.003 77.7% Design Parallel 15 -0.59 -1.04 to -0.13 2.51 0.01 85.5% Cross-over 10 -0.85 -1.13 to -0.57 5.96 <0.001 68.2% Procedure Dressing 12 -0.66 -1.20 to -0.11 2.37 0.02 87.1% Physical therapy 8 -0.63 -0.95 to -0.31 3.84 <0.001 72.2% Debridement 3 -0.91 -1.55 to -0.28 2.81 0.005 77.7% Wound care 0 -0.35 -1.29 to 0.59 0.73 0.46 0 *: number of studies, **: Standard mean difference. CI: confidence interval. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem Introduction Methods Results Discussion Limitations Implications for health managers and policymakers Implications for future research Conclusion Declarations References